Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis

open24siSelenoproteins are rare proteins among all kingdoms of life containing the 21st amino acid, selenocysteine. Selenocysteine resembles cysteine, differing only by the substitution of selenium for sulfur. Yet the actual advantage of selenolate- versus thiolate-based catalysis has remained enigmatic, as most of the known selenoproteins also exist as cysteine-containing homologs. Here, we demonstrate that selenolate-based catalysis of the essential mammalian selenoprotein GPX4 is unexpectedly dispensable for normal embryogenesis. Yet the survival of a specific type of interneurons emerges to exclusively depend on selenocysteine-containing GPX4, thereby preventing fatal epileptic seizures. Mechanistically, selenocysteine utilization by GPX4 confers exquisite resistance to irreversible overoxidation as cells expressing a cysteine variant are highly sensitive toward peroxide-induced ferroptosis. Remarkably, concomitant deletion of all selenoproteins in Gpx4cys/cys cells revealed that selenoproteins are dispensable for cell viability provided partial GPX4 activity is retained. Conclusively, 200 years after its discovery, a specific and indispensable role for selenium is provided.openIngold, Irina; Berndt, Carsten; Schmitt, Sabine; Doll, Sebastian; Poschmann, Gereon; Buday, Katalin; Roveri, Antonella; Peng, Xiaoxiao; Porto Freitas, Florencio; Seibt, Tobias; Mehr, Lisa; Aichler, Michaela; Walch, Axel; Lamp, Daniel; Jastroch, Martin; Miyamoto, Sayuri; Wurst, Wolfgang; Ursini, Fulvio; Arnér, Elias S J; Fradejas-Villar, Noelia; Schweizer, Ulrich; Zischka, Hans; Friedmann Angeli, José Pedro; Conrad, MarcusIngold, Irina; Berndt, Carsten; Schmitt, Sabine; Doll, Sebastian; Poschmann, Gereon; Buday, Katalin; Roveri, Antonella; Peng, Xiaoxiao; Porto Freitas, Florencio; Seibt, Tobias; Mehr, Lisa; Aichler, Michaela; Walch, Axel; Lamp, Daniel; Jastroch, Martin; Miyamoto, Sayuri; Wurst, Wolfgang; Ursini, Fulvio; Arnér, Elias S J; Fradejas-Villar, Noelia; Schweizer, Ulrich; Zischka, Hans; Friedmann Angeli, José Pedro; Conrad, Marcu

Measurement of the charge ratio of atmospheric muons with the CMS detector

This is the pre-print version of this Article. The official published version can be accessed from the link below - Copyright @ 2010 ElsevierWe present a measurement of the ratio of positive to negative muon fluxes from cosmic ray interactions in the atmosphere, using data collected by the CMS detector both at ground level and in the underground experimental cavern at the CERN LHC. Muons were detected in the momentum range from 5 GeV/c to 1 TeV/c. The surface flux ratio is measured to be 1.2766 \pm 0.0032(stat.) \pm 0.0032 (syst.), independent of the muon momentum, below 100 GeV/c. This is the most precise measurement to date. At higher momenta the data are consistent with an increase of the charge ratio, in agreement with cosmic ray shower models and compatible with previous measurements by deep-underground experiments

Observation of a new Xi(b) baryon

The first observation of a new b baryon via its strong decay into Xi(b)^- pi^+ (plus charge conjugates) is reported. The measurement uses a data sample of pp collisions at sqrt(s) = 7 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 5.3 inverse femtobarns. The known Xi(b)^- baryon is reconstructed via the decay chain Xi(b)^- to J/psi Xi^- to mu^+ mu^- Lambda^0 pi^-, with Lambda^0 to p pi^-. A peak is observed in the distribution of the difference between the mass of the Xi(b)^- pi^+ system and the sum of the masses of the Xi(b)^- and pi^+, with a significance exceeding five standard deviations. The mass difference of the peak is 14.84 +/- 0.74 (stat.) +/- 0.28 (syst.) MeV. The new state most likely corresponds to the J^P=3/2^+ companion of the Xi(b).Comment: Submitted to Physical Review Letter

Measurements of inclusive W and Z cross sections in pp collisions at root s=7 TeV

This is the pre-print version of the Published Article, which can be accessed from the link below - Copyright @ 2011 Springer VerlagMeasurements of inclusive W and Z boson production cross sections in pp collisions at sqrt(s)=7 TeV are presented, based on 2.9 inverse picobarns of data recorded by the CMS detector at the LHC. The measurements, performed in the electron and muon decay channels, are combined to give sigma(pp to WX) times B(W to muon or electron + neutrino) = 9.95 \pm 0.07(stat.) \pm 0.28(syst.) \pm 1.09(lumi.) nb and sigma(pp to ZX) times B(Z to oppositely charged muon or electron pairs) = 0.931 \pm 0.026(stat.) \pm 0.023(syst.) \pm 0.102(lumi.) nb. Theoretical predictions, calculated at the next-to-next-to-leading order in QCD using recent parton distribution functions, are in agreement with the measured cross sections. Ratios of cross sections, which incur an experimental systematic uncertainty of less than 4%, are also reported

Search for three-jet resonances in pp collisions at √s=7 TeV

This is a Pre-Print version of the Article - Copyright @ 2011 APSA model-independent search for three-jet hadronic resonance production in pp collisions at a center-of-mass energy of 7 TeV has been conducted by the CMS Collaboration at the LHC, using a data sample corresponding to an integrated luminosity of 35 inverse picobarns. Events with high jet multiplicity and a large scalar sum of jet transverse momenta are analyzed. The number of expected standard model background events is found to be in good agreement with the observed events. Limits are set on a model describing the production of R-parity-violating supersymmetric gluino pairs, and gluino masses in the range of 200 to 280 GeV/c^2 are excluded at a 95% confidence level for the first time.This work is supported by the FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF andWCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Combined measurements of Higgs boson couplings in proton- proton collisions at v s=13TeV

Combined measurements of the production and decay rates of the Higgs boson, as well as its couplings to vector bosons and fermions, are presented. The analysis uses the LHC proton-proton collision data set recorded with the CMS detector in 2016 at fb-1. The combination is based on analyses targeting the five main Higgs boson production mechanisms (gluon fusion, vector boson fusion, and associated production with a W or Z boson, or a top quark-antiquark pair) and the following decay modes: H, ZZ, WW, , bb, and . Searches for invisible Higgs boson decays are also considered. The best-fit ratio of the signal yield to the standard model expectation is measured to be =1.17 +/- 0.10, assuming a Higgs boson mass of 125.09. Additional results are given for various assumptions on the scaling behavior of the production and decay modes, including generic parametrizations based on ratios of cross sections and branching fractions or couplings. The results are compatible with the standard model predictions in all parametrizations considered. In addition, constraints are placed on various two Higgs doublet models.Peer reviewe